TY - JOUR T1 - A Systems Model for Immune Cell Interactions Unravels the Mechanism of Inflammation in Human Skin A1 - Valeyev, Najl V. A1 - Hundhausen, Christian A1 - Umezawa, Yoshinori A1 - Kotov, Nikolay V. A1 - Williams, Gareth A1 - Clop, Alex A1 - Ainali, Crysanthi A1 - Ouzounis, Christos A1 - Tsoka, Sophia A1 - Nestle, Frank O. Y1 - 2010/12/02 N2 - Author Summary A functional immune system requires complex interactions among diverse cell types, mediated by a variety of cytokines. These interactions include phenomena such as positive and negative feedback loops that can be experimentally characterized by dose-dependent cytokine production measurements. However, any experimental approach is not only limited with regard to the number of cell-cell interactions that can be studied at a given time, but also does not have the capacity to assess or predict the overall immune response which is the result of complex interdependent immune cell interactions. Therefore, experimental data need to be viewed from a theoretical perspective allowing the quantitative modeling of immune cell interactions. Here, we propose a strategy for a quantitative description of multiple interactions between immune cell populations based on their cytokine production profiles. The model predicts that the modified feedback loop interactions can result in the appearance of alternative steady-states causing the switch-like immune system effect that is experimentally observed in pathologic phenotypes. Overall, the quantitative description of immune cell interactions via cytokine signaling reported here offers new insights into understanding and predicting normal and pathological immune system responses. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 6 IS - 12 UR - https://doi.org/10.1371/journal.pcbi.1001024 SP - e1001024 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1001024 ER -